Very-long-chain fatty acid elongase Elo2 rescues lethal defects associated with loss of the nuclear barrier function

Author:

Kinuagsa Yasuha1,Hirano Yasuhiro1ORCID,Sawai Megumi2,Ohno Yusuke2ORCID,Shindo Tomoko3,Asakawa Haruhiko1ORCID,Chikashige Yuji4,Shibata Shinsuke3ORCID,Kihara Akio2ORCID,Haraguchi Tokuko14ORCID,Hiraoka Yasushi14ORCID

Affiliation:

1. Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan

2. Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan

3. Electron Microscope Laboratory, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan

4. Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, Kobe 651-2492, Japan

Abstract

In eukaryotic cells, chromosomes are confined to the nucleus, which is compartmentalized by the nuclear membranes. The nuclear membranes are continuous with the endoplasmic reticulum membranes. Maintaining the homeostasis of these membranes is an important cellular activity performed by lipid metabolic enzymes. However, how lipid metabolic enzymes affect nuclear membrane functions remains to be elucidated. We found that the very-long-chain fatty acid elongase Elo2 is localized in the nuclear membrane and prevents lethal defects associated with nuclear membrane ruptures in mutants of the nuclear membrane proteins Lem2 and Bqt4 in the fission yeast Schizosaccharomyces pombe. Lipid composition analysis shows that t20:0/24:0 phytoceramide (a conjugate of C20:0 phytosphingosine and C24:0 fatty acid) is a major ceramide species in S. pombe. The quantity of this ceramide is reduced in the absence of Lem2, and restored by increased expression of Elo2. Furthermore, the loss of S. pombe Elo2 can be rescued by its human orthologs. These results suggest that the conserved very-long-chain fatty acid elongase producing the ceramide component is essential for nuclear membrane integrity and cell viability in eukaryotes.

Funder

Japan Society for the Promotion of Science

Japan Agency for Medical Research and Development

Publisher

The Company of Biologists

Subject

Cell Biology

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